Gap junctions are clusters of intercellular channels allowing the bidirectional pass of ions directly into the cytoplasm of adjacent cells. Electrical coupling mediated by gap junctions plays a role in the generation of highly synchronized electrical activity. The hypersynchronous neuronal activity is a distinctive characteristic of convulsive events. Therefore, it has been postulated that enhanced gap junctional communication is an underlying mechanism involved in the generation and maintenance of seizures. There are some chemical compounds characterized as gap junction blockers because of their ability to disrupt the gap junctional intercellular communication. Hence, the aim of this review is to analyze the available data concerning the effects of gap junction blockers specifically in seizure models. Carbenoxolone, quinine, mefloquine, quinidine, anandamide, oleamide, heptanol, octanol, meclofenamic acid, niflumic acid, flufenamic acid, glycyrrhetinic acid and retinoic acid have all been evaluated on animal seizure models. In vitro, these compounds share anticonvulsant effects typically characterized by the reduction of both amplitude and frequency of the epileptiform activity induced in brain slices. In vivo, gap junction blockers modify the behavioral parameters related to seizures induced by 4-aminopyridine, pentylenetetrazole, pilocarpine, penicillin and maximal electroshock. Although more studies are still required, these molecules could be a promising avenue in the search for new pharmaceutical alternatives for the treatment of epilepsy.

Ozone (O3) is a component of photochemical smog, which is a major air pollutant and demonstrates properties that are harmful to health because of the toxic properties that are inherent to its powerful oxidizing capabilities. Environmental O3 exposure is associated with many symptoms related to respiratory disorders, which include loss of lung function, exacerbation of asthma, airway damage, and lung inflammation. The effects of O3 are not restricted to the respiratory system or function - adverse effects within the central nervous system (CNS) such as decreased cognitive response, decrease in motor activity, headaches, disturbances in the sleep-wake cycle, neuronal dysfunctions, cell degeneration, and neurochemical alterations have also been described; furthermore, it has also been proposed that O3 could have epigenetic effects. O3 exposure induces the reactive chemical species in the lungs, but the short half-life of these chemical species has led some authors to attribute the injurious mechanisms observed within the lungs to inflammatory processes. However, the damage to the CNS induced by O3 exposure is not well understood. In this review, the basic mechanisms of inflammation and activation of the immune system by O3 exposure are described and the potential mechanisms of damage, which include neuroinflammation and oxidative stress, and the signs and symptoms of disturbances within the CNS caused by environmental O3 exposure are discussed.

Cranial irradiation remains a standard treatment for malignant and benign brain diseases. Although this procedure helps to lengthen the life expectancy of the patient, the appearance of adverse effects related to radiationinduced injury is inevitable. Radiation somnolence syndrome (RSS) has been described as a delayed effect observed mainly after whole-brain radiotherapy in children. The RSS was first linked to demyelination, but more recently it has been proposed that the inflammatory response plays a primary role in the aforementioned syndrome. To evaluate the feasibility of this hypothesis, we explored previous work about RSS and reviewed published research that included measurements of the inflammatory response in models of brain exposure to ionizing radiation. Pro-inflammatory cytokines such as interleukin-1β, tumor necrosis factor-α, interleukin-6 and interleukin-18 as well as other inflammatory markers such as cyclooxygenase-2, prostaglandin E2, glial fibrillary acid protein, intercellular adhesion molecule-1 and nuclear factor-κB appear to be involved in the brain’s response to radiation. However, certain publications have described the somnogenic effects of these cytokines and inflammatory markers. Although the radiation response is a complex phenomenon that involves several molecular and cellular processes, we propose that inflammation may be closely related to the adverse effects of brain irradiation and therefore to the etiology of RSS.

Some reports have described that a high fructose diet is associated with a deficit of hippocampus-dependent cognitive functions. In this study, we have evaluated the effects of fructose on spatial memory and molecular markers in the hippocampus and prefrontal cortex and analyzed whether those alterations are reversible. Male Wistar rats (n = 60) began their treatment during adolescence. A group was forced to drink a solution of 10% fructose for twelve weeks. Another group was subjected to the same fructose intake schedule, but later fructose was removed, and tap water was provided for four weeks. After treatments, spatial memory was evaluated with Barnes maze. Different neurogenesis, inflammation, astrocyte, and energy homeostasis markers were evaluated with immunofluorescence, ELISA, and Western blot. Changes were analyzed using two-way repeated-measures ANOVA, one-way ANOVA, and Tukeýs posthoc test (p < 0.05). Results showed that after long-term consumption of fructose, there was an impairment of spatial memory. This deficit was concomitant with the abolition of hippocampal neurogenesis and significant increases of IL-1b in the hippocampus and prefrontal cortex. Levels of COX-2 were decreased in the hippocampus. Besides, fructose induced a significant increase in GFAP and a decrease of glutamine synthetase. Likewise, energy homeostasis-associated neuropeptide orexin-A and their receptors (ORX R1 and ORX R2) were significantly increased. The spatial memory deficit, neuroinflammation, and changes in some proteinś expression were permanent one month after the fructose elimination from the diet. These results suggest that fructose induces substantial hippocampal and cortical changes, and those are irreversible after a shift in the diet.

Gap junctional communication is mainly mediated by connexin36 and connexin43 in neurons and astrocytes, respectively. It has been suggested that connexin36 allows electrical coupling between neurons whereas connexin43 participates in several process including release of ATP. It was recently reported that blockage of gap junctional communication mediated by connexin36 can disrupt the sleep architecture of the rat. However, there is no experimental approach about effects of sleep deprivation on connexins expression. Therefore, we examined in adult male Wistar rats whether protein levels of connexin36 and connexin43 change in pons, hypothalamus, and frontal cortex after 24 h of total sleep deprivation and 4 h of sleep recovery. Western blot revealed that total sleep deprivation significantly decreases the levels of connexin36 in the hypothalamus and this decrease maintains after sleep recovery. Meanwhile, connexin43 is not altered by total sleep deprivation but interestingly the sleep recovery period induces an increase of this connexin. These results suggest that electrical coupling between hypothalamic neurons could be altered by sleep deprivation and that sleep recovery drives changes in connexin43 expression probably as a mechanism related to ATP release and energy regulation during sleep.